Visualizing the Structure and Motion of the Long Noncoding RNA HOTAIR

Overview

Journal RNA

Specialty Molecular Biology

Date 2020 Mar 3

PMID 32115425

Citations 18

Authors

Rachel Spokoini-Stern

Dimitar Stamov

Hadass Jessel

Lior Aharoni

Heiko Haschke

Jonathan Giron

Ron Unger

Eran Segal

Almogit Abu-Horowitz

Ido Bachelet

Affiliations

Soon will be listed here.

Abstract

Long noncoding RNA molecules (lncRNAs) are estimated to account for the majority of eukaryotic genomic transcripts, and have been associated with multiple diseases in humans. However, our understanding of their structure-function relationships is scarce, with structural evidence coming mostly from indirect biochemical approaches or computational predictions. Here we describe direct visualization of the lncRNA HOTAIR (HOx Transcript AntIsense RNA) using atomic force microscopy (AFM) in nucleus-like conditions at 37°. Our observations reveal that HOTAIR has a discernible, although flexible, shape. Fast AFM scanning enabled the quantification of the motion of HOTAIR, and provided visual evidence of physical interactions with genomic DNA segments. Our report provides a biologically plausible description of the anatomy and intrinsic properties of HOTAIR, and presents a framework for studying the structural biology of lncRNAs.

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References

Novikova I, Hennelly S, Sanbonmatsu K . Structural architecture of the human long non-coding RNA, steroid receptor RNA activator. Nucleic Acids Res. 2012; 40(11):5034-51. PMC: 3367176. DOI: 10.1093/nar/gks071. View

Fatica A, Bozzoni I . Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet. 2013; 15(1):7-21. DOI: 10.1038/nrg3606. View

Cowan J . Structural and catalytic chemistry of magnesium-dependent enzymes. Biometals. 2002; 15(3):225-35. DOI: 10.1023/a:1016022730880. View

Andersen E, Antoranz Contera S, Knudsen B, Damgaard C, Besenbacher F, Kjems J . Role of the trans-activation response element in dimerization of HIV-1 RNA. J Biol Chem. 2004; 279(21):22243-9. DOI: 10.1074/jbc.M314326200. View

Novikova I, Hennelly S, Sanbonmatsu K . Tackling structures of long noncoding RNAs. Int J Mol Sci. 2013; 14(12):23672-84. PMC: 3876070. DOI: 10.3390/ijms141223672. View

Lyubchenko Y, Shlyakhtenko L, Ando T . Imaging of nucleic acids with atomic force microscopy. Methods. 2011; 54(2):274-83. PMC: 3114274. DOI: 10.1016/j.ymeth.2011.02.001. View

Brown J, Bulkley D, Wang J, Valenstein M, Yario T, Steitz T . Structural insights into the stabilization of MALAT1 noncoding RNA by a bipartite triple helix. Nat Struct Mol Biol. 2014; 21(7):633-40. PMC: 4096706. DOI: 10.1038/nsmb.2844. View

Wu Z, Wang X, Tang H, Jiang T, Chen J, Lu S . Long non-coding RNA HOTAIR is a powerful predictor of metastasis and poor prognosis and is associated with epithelial-mesenchymal transition in colon cancer. Oncol Rep. 2014; 32(1):395-402. DOI: 10.3892/or.2014.3186. View

Rinn J, Kertesz M, Wang J, Squazzo S, Xu X, Brugmann S . Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell. 2007; 129(7):1311-23. PMC: 2084369. DOI: 10.1016/j.cell.2007.05.022. View

10.

Hagerman P . Flexibility of RNA. Annu Rev Biophys Biomol Struct. 1997; 26:139-56. DOI: 10.1146/annurev.biophys.26.1.139. View

11.

Wutz A, Rasmussen T, Jaenisch R . Chromosomal silencing and localization are mediated by different domains of Xist RNA. Nat Genet. 2002; 30(2):167-74. DOI: 10.1038/ng820. View

12.

Ban N, Nissen P, Hansen J, Moore P, Steitz T . The complete atomic structure of the large ribosomal subunit at 2.4 A resolution. Science. 2000; 289(5481):905-20. DOI: 10.1126/science.289.5481.905. View

13.

Liu X, Liu Z, Sun M, Liu J, Wang Z, De W . The long non-coding RNA HOTAIR indicates a poor prognosis and promotes metastasis in non-small cell lung cancer. BMC Cancer. 2013; 13:464. PMC: 3851855. DOI: 10.1186/1471-2407-13-464. View

14.

DICKERSON R . Base sequence and helix structure variation in B and A DNA. J Mol Biol. 1983; 166(3):419-41. DOI: 10.1016/s0022-2836(83)80093-x. View

15.

Alves C, Fonseca A, Muys B, de Barros E Lima Bueno R, Burger M, de Souza J . Brief report: The lincRNA Hotair is required for epithelial-to-mesenchymal transition and stemness maintenance of cancer cell lines. Stem Cells. 2013; 31(12):2827-32. DOI: 10.1002/stem.1547. View

16.

Buske F, Bauer D, Mattick J, Bailey T . Triplexator: detecting nucleic acid triple helices in genomic and transcriptomic data. Genome Res. 2012; 22(7):1372-81. PMC: 3396377. DOI: 10.1101/gr.130237.111. View

17.

Dinger M, Amaral P, Mercer T, Pang K, Bruce S, Gardiner B . Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. Genome Res. 2008; 18(9):1433-45. PMC: 2527704. DOI: 10.1101/gr.078378.108. View

18.

Wu L, Murat P, Matak-Vinkovic D, Murrell A, Balasubramanian S . Binding interactions between long noncoding RNA HOTAIR and PRC2 proteins. Biochemistry. 2013; 52(52):9519-27. PMC: 3964825. DOI: 10.1021/bi401085h. View

19.

Amaral P, Mattick J . Noncoding RNA in development. Mamm Genome. 2008; 19(7-8):454-92. DOI: 10.1007/s00335-008-9136-7. View

20.

Hung T, Chang H . Long noncoding RNA in genome regulation: prospects and mechanisms. RNA Biol. 2010; 7(5):582-5. PMC: 3073254. DOI: 10.4161/rna.7.5.13216. View